The Effect of Glitazone Treatment on Bone Marrow and Bone Marrow Cells - Full Text View

Sponsor:	University of Aarhus
Information provided by:	University of Aarhus
ClinicalTrials.gov Identifier:	NCT00609362

Purpose

Osteoporosis is a generalised bone disease leading to an increased risk of fractures. The disease is caused partly by environmental and partly by genetic factors. It is well known that the fat content of the bone marrow is increased in osteoporotic patients. Animal studies suggest that stimulation of bone marrow stem cells through the molecule PPARgamma with the drug rosiglitazone converts the stem cells to fat cells instead of bone cells thereby decreasing bone strength. In a single study healthy volunteers were treated with rosiglitazone for 14 weeks and had a decrease in bone mineral density.

In the present study we wish to investigate the effect of this treatment on bone and fat tissue. 25 women above the age of 60 will be treated with rosiglitazone 8 mg/day for 14 weeks and compared with 25 women receiving placebo.

The effect will be evaluated as follows:

The effect on bone marrow density will be examined by a bone scan prior to and after treatment and again after 6 and 9 months.
The effect on bone turnover will be measured in blood- and urine samples at the same times.
The effect on fat distribution will be evaluated by an MRI scan after treatment.
The effect on bone marrow cells will be investigated bone marrow sampling immediately after treatment
The direct effect on fat will be examined by a biopsy immediately after treatment The study hypothesis is that rosiglitazone treatment decreases bone mineral density and increases bone marrow fat content. The causal molecular mechanisms will be investigated from the bone marrow and fat samples

Condition	Intervention	Phase
Change in Bone Mineral Density Change in Bone Marrow Fat Content	Drug: Rosiglitazone Drug: Placebo pill	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacodynamics Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Basic Science
Official Title:	The Effect of Glitazone Treatment on Bone Marrow and Bone Marrow Cells

Resource links provided by NLM:

MedlinePlus related topics: Bone Density Minerals

Drug Information available for: Rosiglitazone Rosiglitazone Maleate

U.S. FDA Resources

Further study details as provided by University of Aarhus:

Primary Outcome Measures:

Difference in Percent Change in Bone Mineral Density (BMD) From Baseline to 14 Weeks Between the Rosiglitazone Group and the Placebo Group [ Time Frame: BMD measured at baseline and after 14 weeks of treatment ] [ Designated as safety issue: No ]
Difference in percent change in bone mineral density (BMD) from baseline to 14 weeks between the rosiglitazone group and the placebo group. BMD was assesed using dual x-ray absorptiometry (DXA)

Secondary Outcome Measures:

Difference in Percent Change in Bone Marrow Fat (Given by a Lipid to Water Ratio) in the Spine. [ Time Frame: Measured at baseline and after 14 weeks of treatment ] [ Designated as safety issue: No ]
Bone marrow fat was measured using MRI spectroscopy providing a measure of bone marrow fat as a ratio to bone marrow water, the lipid-water ratio (LWR)
Difference in Percent Change in Level of C-terminal Telopeptide (CTx) Between the Rosiglitazone and Placebo Groups [ Time Frame: At baseline and after 14 weeks of treatment ] [ Designated as safety issue: No ]
C-terminal telopeptide is a marker of bone resorption. Its levels are measure in plasma using a chemiluminometric method (ECLIA).
Change in Gene Expression in Bone Marrow and Fat Cells [ Time Frame: Before and after treatment ] [ Designated as safety issue: No ]

Enrollment:	57
Study Start Date:	January 2008
Study Completion Date:	November 2009
Primary Completion Date:	November 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Rosiglitazone 25 women age 60 to 75 years receiving rosiglitazone 8 mg/day	Drug: Rosiglitazone one tablet of rosiglitazone 8 milligrams per day for 14 weeks Other Name: Avandia
Placebo Comparator: Placebo 25 women 60 to 75 years of age receiving placebo once a day for 14 weeks	Drug: Placebo pill One encapsulated placebo pill a day for 14 weeks

Eligibility

Ages Eligible for Study:	60 Years to 75 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Postmenopausal women age 60-75 with no rosiglitazone allergy

Exclusion Criteria:

Osteoporosis
Diabetes
Hyperthyroidism, untreated hypothyroidism, hyperparathyroidism
Treatment with bone active drugs
Low impact fracture
Heart disease
Kidney failure
Liver failure
Anaemia
Ineligibility for MRI-scan
Cancer within last 5 years

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00609362

Locations

Denmark
Aarhus University Hospital
Aarhus, Denmark, 8000 C

Sponsors and Collaborators

University of Aarhus

Investigators

Principal Investigator:

Torben Harsløf, Dr.

Aarhus University Hospital

More Information

No publications provided

Responsible Party:	Bente Langdahl, Aarhus University Hospital
ClinicalTrials.gov Identifier:	NCT00609362 History of Changes
Other Study ID Numbers:	2007-223
Study First Received:	January 24, 2008
Results First Received:	February 17, 2011
Last Updated:	March 29, 2011
Health Authority:	Denmark: The Danish National Committee on Biomedical Research Ethics

Keywords provided by University of Aarhus:

BMD
Rosiglitazone
Bone marrow fat

Additional relevant MeSH terms:

Rosiglitazone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012